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Brain heterotopia formation by ciliopathic breakdown of neuroepithelial and blood‐cerebrospinal fluid barriers
The developmental functions of primary cilia and the downstream signaling pathways have been widely studied; however, the roles of primary cilia in the developing neurovascular system are not clearly understood. In this study, we found that ablation of genes encoding ciliary transport proteins such...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10307530/ https://www.ncbi.nlm.nih.gov/pubmed/36623505 http://dx.doi.org/10.1111/bpa.13148 |
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author | Jung, Hyun Jin Yeo, Seungeun Jang, Jaemyung Pleasure, Samuel Choe, Youngshik |
author_facet | Jung, Hyun Jin Yeo, Seungeun Jang, Jaemyung Pleasure, Samuel Choe, Youngshik |
author_sort | Jung, Hyun Jin |
collection | PubMed |
description | The developmental functions of primary cilia and the downstream signaling pathways have been widely studied; however, the roles of primary cilia in the developing neurovascular system are not clearly understood. In this study, we found that ablation of genes encoding ciliary transport proteins such as intraflagellar transport homolog 88 (Ift88) and kinesin family member 3a (Kif3a) in cortical radial progenitors led to periventricular heterotopia during late mouse embryogenesis. Conditional mutation of primary cilia unexpectedly caused breakdown of both the neuroepithelial lining and the blood‐choroid plexus barrier. Choroidal leakage was partially caused by enlargement of the choroid plexus in the cilia mutants. We found that the choroid plexus expressed platelet‐derived growth factor A (Pdgf‐A) and that Pdgf‐A expression was ectopically increased in cilia‐mutant embryos. Cortices obtained from embryos in utero electroporated with Pdgfa mimicked periventricular heterotopic nodules of the cilia mutant. These results suggest that defective ciliogenesis in both cortical progenitors and the choroid plexus leads to breakdown of cortical and choroidal barriers causing forebrain neuronal dysplasia, which may be related to developmental cortical malformation. |
format | Online Article Text |
id | pubmed-10307530 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-103075302023-06-30 Brain heterotopia formation by ciliopathic breakdown of neuroepithelial and blood‐cerebrospinal fluid barriers Jung, Hyun Jin Yeo, Seungeun Jang, Jaemyung Pleasure, Samuel Choe, Youngshik Brain Pathol Research Articles The developmental functions of primary cilia and the downstream signaling pathways have been widely studied; however, the roles of primary cilia in the developing neurovascular system are not clearly understood. In this study, we found that ablation of genes encoding ciliary transport proteins such as intraflagellar transport homolog 88 (Ift88) and kinesin family member 3a (Kif3a) in cortical radial progenitors led to periventricular heterotopia during late mouse embryogenesis. Conditional mutation of primary cilia unexpectedly caused breakdown of both the neuroepithelial lining and the blood‐choroid plexus barrier. Choroidal leakage was partially caused by enlargement of the choroid plexus in the cilia mutants. We found that the choroid plexus expressed platelet‐derived growth factor A (Pdgf‐A) and that Pdgf‐A expression was ectopically increased in cilia‐mutant embryos. Cortices obtained from embryos in utero electroporated with Pdgfa mimicked periventricular heterotopic nodules of the cilia mutant. These results suggest that defective ciliogenesis in both cortical progenitors and the choroid plexus leads to breakdown of cortical and choroidal barriers causing forebrain neuronal dysplasia, which may be related to developmental cortical malformation. John Wiley and Sons Inc. 2023-01-09 /pmc/articles/PMC10307530/ /pubmed/36623505 http://dx.doi.org/10.1111/bpa.13148 Text en © 2023 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Research Articles Jung, Hyun Jin Yeo, Seungeun Jang, Jaemyung Pleasure, Samuel Choe, Youngshik Brain heterotopia formation by ciliopathic breakdown of neuroepithelial and blood‐cerebrospinal fluid barriers |
title | Brain heterotopia formation by ciliopathic breakdown of neuroepithelial and blood‐cerebrospinal fluid barriers |
title_full | Brain heterotopia formation by ciliopathic breakdown of neuroepithelial and blood‐cerebrospinal fluid barriers |
title_fullStr | Brain heterotopia formation by ciliopathic breakdown of neuroepithelial and blood‐cerebrospinal fluid barriers |
title_full_unstemmed | Brain heterotopia formation by ciliopathic breakdown of neuroepithelial and blood‐cerebrospinal fluid barriers |
title_short | Brain heterotopia formation by ciliopathic breakdown of neuroepithelial and blood‐cerebrospinal fluid barriers |
title_sort | brain heterotopia formation by ciliopathic breakdown of neuroepithelial and blood‐cerebrospinal fluid barriers |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10307530/ https://www.ncbi.nlm.nih.gov/pubmed/36623505 http://dx.doi.org/10.1111/bpa.13148 |
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